The ultimate challenge of tissue engineering research is the translation of experimental knowledge into clinical application. In the preclinical testing phase of any new therapy, animal models remain the gold standard. Therefore, the methodological choice of a suitable model is critical to meet the requirements for a safe clinical application of the developed treatment. For instance, we have shown in rats that the application of calcium phosphate cement (CPC)/propylene glycol alginate (PGA) with bone morphogenetic protein (BMP)-2 or fibroblast growth factor (FGF)-2 resulted in the regeneration of periodontal defects. However, it is debated whether using small models form a predictive method for translation to larger species. At the same time, the 3R framework is encouraged as guiding principles of the ethical use of animal testing. Therefore, based on the successful rat study, the objective of this study was to further investigate the periodontal regenerative efficacy of the CPC/BMP and PGA/FGF system in a periodontal defect model with a low number of nonhuman primates (NHPs). Three Macaca fascicularis-overstocked from breeding for other purposes-were used (reuse of animals and appropriateness of the experimental animal species according to 3R framework). Three-wall periodontal defects were surgically created in the mandible. In total, 10 defects were created and distributed over two groups: (1) control group: PGA+CPC (n = 5) and (2) experimental group: PGA/FGF+CPC/BMP (n = 5). After 3 months, tissue regeneration was evaluated by histomorphometry and radiographic measurements. Data showed that epithelial downgrowth, cementum, and ligament regeneration were significantly enhanced in the experimental group compared with the control group (n = 5; p = 0.013, p = 0.028, and p = 0.018, respectively). However, the amount of newly formed bone did not differ (p = 0.146). Overall, as a translational proof-of-principle study, the hybrid periodontal regenerative method of CPC/BMP+PGA/FGF promoted periodontal regeneration in NHPs. This study warrants the application of CPC/BMP/PGA/FGF in clinical trials. Impact Statement This study validated an earlier successful periodontal regeneration strategy from a rat model into a few spare nonhuman primates (NHPs). The hybrid periodontal regenerative method of calcium phosphate cement (CPC)/bone morphogenetic protein (BMP)-2/propylene glycol alginate (PGA)/fibroblast growth factor (FGF)-2 promoted periodontal regeneration in NHPs, which corroborated the previous rat results. This translational approach was a very practical option and thus reduced the number and species of experimental animals in translational research. These results found in NHPs indicate a consistent conclusion with the earlier findings in the rat model. It further warrants the application of CPC/BMP-2+PGA/FGF-2 in human clinical trials.

中文翻译：

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BMP骨水泥和FGF-Gel在非人类灵长类动物牙周组织再生中的应用。

组织工程研究的最终挑战是将实验知识转化为临床应用。在任何新疗法的临床前测试阶段，动物模型仍然是金标准。因此，合适模型的方法选择对于满足已开发治疗的安全临床应用要求至关重要。例如，我们已经在大鼠中表明，将磷酸钙水泥（CPC）/藻酸丙二醇酯（PGA）与骨形态发生蛋白（BMP）-2或成纤维细胞生长因子（FGF）-2一起使用可导致牙周缺损的再生。但是，使用小模型是否构成翻译成较大物种的预测方法存在争议。同时，鼓励将3R框架作为动物测试在伦理上使用的指导原则。因此，基于成功的大鼠研究，本研究的目的是进一步研究CPC / BMP和PGA / FGF系统在具有少量非人类灵长类动物（NHP）的牙周缺损模型中的牙周再生功效。使用了三个因其他目的而从繁殖中积压的猕猴（根据3R框架对动物进行再利用和实验动物物种的适宜性）。手术切除下颌骨中的三层牙周缺损。总共创建了10个缺陷并将其分布在两组中：（1）对照组：PGA + CPC（n = 5）和（2）实验组：PGA / FGF + CPC / BMP（n = 5）。3个月后，通过组织形态测定法和射线照相术评估组织再生。数据显示上皮下生长，牙骨质，与对照组相比，实验组的韧带和韧带再生显着增强（n = 5； p = 0.013，p = 0.028和p = 0.018）。但是，新形成的骨骼数量没有差异（p = 0.146）。总体而言，作为转化原则的研究，CPC / BMP + PGA / FGF的混合牙周再生方法促进了NHP中的牙周再生。这项研究保证了CPC / BMP / PGA / FGF在临床试验中的应用。影响陈述这项研​​究验证了较早成功的从大鼠模型成功转化为少量非人类灵长类动物（NHP）的牙周再生策略。磷酸钙水泥（CPC）/骨形态发生蛋白（BMP）-2 /藻酸丙二醇酯（PGA）/成纤维细胞生长因子（FGF）-2的混合牙周再生方法可促进NHP中的牙周再生，这证实了先前的大鼠结果。这种翻译方法是非常实用的选择，因此减少了翻译研究中实验动物的数量和种类。在NHP中发现的这些结果表明与大鼠模型中的早期发现具有一致的结论。它进一步保证了CPC / BMP-2 + PGA / FGF-2在人类临床试验中的应用。